Alcohol consumption is associated with a higher viral set point in SIV-infected rhesus macaques. We hypothesize that alcohol consumption will also correlate with increased viral expression in seminal fluid of macaques, causing persistent virus expression or intermittent shedding of high titers of virus in semen. We also hypothesize that increased viral replication in seminal fluid will correlate with the development of distinct populations of viral genotypes in semen as compared to blood. We will test these hypotheses in the well- controlled SIV-macaque model to decipher the variables influencing seminal virus expression. In these studies, viral levels will be quantitated by real-time RT-PCR from sequential seminal fluid samples collected throughout the disease course of alcohol-consuming and sucrose-treated control macaques. Viral genotypes expressed in seminal fluid of alcohol-treated animals will also be characterized by sequence analysis and the diversity of viral genotypes in semen and blood with be evaluated with heteroduplex tracking assays. These studies will compare genotypes expressed in various compartments throughout the disease course. These preliminary studies will begin to decipher the correlates of seminal virus expression, determine the effect of alcohol consumption, and aid in the development of specific strategies to prevent transmission and disease progression.